Aminoadamantane derivatives as therapeutic agents

Abstract

The present invention provides novel aminoadamantane derivatives, methods of making the derivatives, compositions including the novel aminoadamantane derivatives, and methods for the treatment and prevention of neurological diseases using the derivatives and compositions. There are a variety of neurological disorders that can be treated using the present invention, including, for example, the following: neurological disorders arising from trauma, ischemic or hypoxic conditions that can be treated include stroke, hypoglycemia, cerebral ischemia, cardiac arrest, spinal cord trauma, head trauma, perinatal hypoxia, cardiac arrest and hypoglycemic neuronal damage; neurodegenerative disorders such as epilepsy, Alzheimer's disease, Huntington's disease Parkinsonism, and amyotrophic lateral sclerosis; other diseases or disorders such as convulsion, pain, depression, anxiety, schizophrenia, muscle spasms, migraine headaches, urinary incontinence, nicotine withdrawal, opiate tolerance and withdrawal, emesis, brain edema, tardive dyskinesia, AIDS-induced dementia, ocular damage, retinopathy, cognitive disorders, and neuronal injury associated with HIV-infection such as dysfunction in cognition, movement and sensation.

What is claimed is:  
     
       1. A method of treating a neurological disorder comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound having the formula:                    
       wherein R 1  is H, alkyl, heteroalkyl, aryl, heteroaryl, C(O)OR 6 , or C(O)R 6 ; R 2  is H, alkyl, heteroalkyl, aryl, heteroaryl, C(O)OR 6  or C(O)R 6 ; R 3  is H, alkyl, heteroalkyl, aryl or heteroaryl; R 4  is H, alkyl, heteroalkyl, aryl, or heteroaryl; R 5  is OR 7  alkyl-OR 7  or heteroalkyl-OR 7 ; R 6  is alkyl, heteroalkyl, aryl or heteroaryl; R 7  is NO 2 , C(O)R 6 , C(O)alkyl-ONO 2  or C(O)heteroalkyl-ONO 2 , and a pharmaceutically acceptable carrier. 
     
     
       2. A method according to  claim 1 , wherein the neurological disorder is selected from the group consisting of cerebal ischemia, Alzheimer's disease, and, Parkinsonism. 
     
     
       3. A method of treating a neurological disorder comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound having the formula:                    
       wherein R 1  is H, alkyl, heteroalkyl, aryl, heteroaryl, C(O)OR 6 , or C(O)R 6 ; R 2  is H; R 3  and R 4  are H or alkyl; R 5  is OR 7 ; and R 7  is NO 2  or C(O)alkyl-ONO 2 . 
     
     
       4. A method of treating a neurological disorder comprising administration to a patient in need of such treatment of a non-toxic therapeutically effective amount of a compound having the formula:                    
       wherein R 1  and R 2  are H; R 3  and R 4  are H or alkyl; R 5  is OR 7 ; and R 7  is NO 2  or C(O)alkyl-ONO 2 .